Fatty acids, C16-18, stearyl esters

Endpoint summary

Description of key information

Skin, rabbit (read across, similar or according to OECD 404): not irritating

Skin, human data (read across): not irritating

Eye, rabbit (read across, similar or according to OECD 405): not irritating

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3

Remarks:

individual mean of readings at

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 93803-87-3

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Remarks:

individual mean of readings at

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 93803-87-3

In vivo skin irritation data from the source substance 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) was selected as key result for reasons of structural similarity and data reliability. Additional in vivo data on skin irritation was available for the source substances Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7) and 2-octyldodecyl myristate (CAS 22766-83-2). For both substances no indication for skin irritating potential was found in rabbits. Additional human data from a single exposure patch test with 11 volunteers indicated that the source substance Docosyl docosanoate (CAS 17671-27-1) was not a skin irritant.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

The read across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their skin irritation potential. No in vivo skin irritation potential was found in rabbit studies for the three source substances 2-octyldodecyl isooctadecanoate (CAS 93803-87-3), Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7) and 2-octyldodecyl myristate (CAS 22766-83-2). Additional human data from a single exposure patch test with 11 volunteers indicated that the source substance Docosyl docosanoate (CAS 17671-27-1) was not a skin irritant. Therefore, no skin irritation potential is expected for target substance Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation, other

Remarks:

in vivo and in vitro/ex vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Remarks:

Summary of available data used for the endpoint assessment of the target substance

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

other: all 6 animals

Remarks:

individual mean of readings at

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 90990-29-7

Irritation parameter:

iris score

Basis:

other: all 6 animals

Remarks:

individual mean of readings at

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 90990-29-7

Irritation parameter:

conjunctivae score

Basis:

animal: #1, #4 and #5

Remarks:

individual mean of readings at

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 90990-29-7

Irritation parameter:

conjunctivae score

Basis:

animal: #2, #3 and #6

Remarks:

individual mean of readings at

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: Source: CAS 90990-29-7

Irritation parameter:

chemosis score

Basis:

animal: #2, #3, #4 and #5

Remarks:

individual mean of readings at

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

other: Source: CAS 90990-29-7

Irritation parameter:

chemosis score

Basis:

animal #1

Remarks:

individual mean of readings at

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: Source: CAS 90990-29-7

Irritation parameter:

chemosis score

Basis:

animal #6

Remarks:

individual mean of readings at

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 h

Remarks on result:

other: Source: CAS 90990-29-7

In vivo eye irritation data from the source substance Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7) was selected as key result for reasons of structural similarity and data reliability. Additional in vivo data on eye irritation in rabbits was available for the source substances 2-octyldodecyl isooctadecanoate (CAS 93803-87-3), Hexadecanoic acid, -isooctadecyl ester (CAS 72576-80-8), and 2-octyldodecyl myristate (CAS 22766-83-2). For all source substances no indication for eye irritating potential was found in rabbits.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008.

Conclusions:

The read across approach is justified in the analogue justification. The target and source substances are considered unlikely to differ in their eye irritation potential. No in vivo eye irritation potential was found in rabbit studies for the four source substances Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7), 2-octyldodecyl isooctadecanoate (CAS 93803-87-3), Hexadecanoic acid, -isooctadecyl ester (CAS 72576-80-8), and 2-octyldodecyl myristate (CAS 22766-83-2). Therefore, no eye irritation potential is expected for target substance Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for read-across

There are no adequate study data on the skin and eye irritation effects of Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5). The assessment was therefore based on studies conducted with analogue substances as part of a read across approach, which is in accordance with Regulation (EC) No. 1907/2006, Annex XI, 1.5. For each specific endpoint the source substance(s) structurally closest to the target substance is/are chosen for read-across, with due regard to the requirements of adequacy and reliability of the available data. Structural similarities and similarities in properties and/or activities of the source and target substance are the basis of read-across. A detailed justification for the analogue read-across approach is provided in the technical dossier (see IUCLID Section 13).

Skin irritation 

CAS 93803-87-3

A study was performed according to OECD guideline 404 to assess the skin irritation potential of 2-octyldodecyl isooctadecanoate (CAS 93803-87-3) (key study, 1998). 0.5 g test substance was applied to the shaved skin of rabbits under semi-occlusive conditions for 4 hours. 3/3 animals had well-defined erythema (score 2) at the 1-hr reading time point. The erythema had reduced in severity by 24 hours after exposure in 3/3 rabbits (score 1, 1, 1), and had cleared completely within 72 hours for 3/3 rabbits. The individual mean erythema scores over the 24, 48 and 72 evaluation times were 0.67, 0.33 and 0.33, respectively.The individual mean erythema and oedema scores over 24/48/72-hour readings were 0.0 for each rabbit. Based on the results of this study, the test substance is not considered to be skin irritating.

CAS 90990-29-7

A skin irritation study was performed with Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7) (supporting study, 1982). No current guideline was followed. 0.5 mL of the undiluted test substance was applied to the clipped or clipped and abraded skin of 6 New Zealand White rabbits and held in place by an occlusive dressing for 24 h. The severity of erythema and oedema was scored 1 and 48 h after patch removal. The test material produced minimal erythema (score 1) in 1/6 rabbits at the intact test site and in 2/6 rabbits at the abraded test site, respectively, 1 h after patch removal. All skin irritation effects were reversible within 48 h after patch removal. No other skin irritation effects were observed in any animal (6/6) at any reading time point. No readings at 72 hours were done, but all skin reading scores were zero at the 48-hour reading. Based on the results of this study, the test substance is not considered to be skin irritating.

 

CAS 22766-83-2

A skin irritation study equivalent to OECD guideline 404 (supporting study, 1986) was performed with 2-octyldodecyl myristate (CAS 22766-83-2). 0.5 mL of the undiluted liquid test substance was applied to the shaved intact and abraded skin of 6 male rabbits for 24 hours of exposure under occlusive conditions. Readings were done at 24 and 72 hours. No oedema was found at any reading. The individual mean oedema scores over 24/72-hour readings were 0.0 for each rabbit. The individual mean erythema scores as 24/48/72-hour readings were calculated in a worst case approach taking the 24-hour value to replace the missing 48-hour values. The individual mean erythema scores as 24/48/72-hour readings were 0.0 in two rabbits, 0.67 in 3 rabbits and 1.0 in one rabbit. Based on the results of this study, the test substance is not considered to be skin irritating.

 

Human data

CAS 17671-27-1

In a single exposure patch test (supporting study, 2005) the undiluted Docosyl docosanoate (CAS 17671-27-1) was applied to the back skin of 11 volunteers for 24 h under occlusive conditions. The skin irritation effects (erythema and edema) were assessed 30 minutes and 24 h after patch removal. Slight to moderate erythema (score 1-1.5) was observed at the test site in 3/10 subjects at the 30-minute reading time point and in 1/10 subjects 24 h after patch removal. The positive control (1% sodium sulphate) was shown to be valid. 1/11 subjects were excluded as moderate erythema was noted at the negative control site (water). The test substance was not a skin irritant under the chosen test conditions.

 

Eye irritation

CAS 90990-29-7

The eye irritation potential of Fatty acids, C16 and C18-22 - unsatd., C16-18 and C18 unsatd. alkyl ester (CAS 90990-29-7) was investigated in six albino rabbits, following a protocol similar to OECD guideline 405 (key study, 1982) and in compliance with GLP. 0.1 g of the test substance was instilled into one eye of each animal. The other eye remained untreated and served as control. The eyes were examined and scored according to the Draize scoring system 24, 48 and 72 h after application. 3/6 animals showed conjunctival redness (score 1) 24 and 48 h after instillation, reversible within 72 h. 2/6 animals showed conjunctivae chemosis (score 1) 24 h after instillation of test substance, in one animal reversible within 48 h, in the second animal reversible within 72 h. The cornea and iris were not affected. The mean 24/48/72 h scores of all 6 animals for redness were 0.0, 0.67, 0.67, 0.0, 0.0 and 0.67, respectively , while mean 24/48/72 h scores for chemosis were 0.67, 0.0, 0.0, 0.0, 0.0 and 0.33, respectively. Based on the results of this study, the test substance is not considered to be irritating to the eyes.

CAS 93803-87-3

2-octyldodecyl isooctadecanoate (CA 93803-87-3) was examined for its eye irritation potential in a GLP study performed according to OECD guideline 405 (supporting study, 1998). 0.1 mL of undiluted test liquid test substance was instilled into one eye of each of 3 rabbits. The animals were observed for 72 hours and scoring according to Draize was performed 1, 24, 48, and 72 hours after application. At the 1-hour reading time point 3/3 rabbits had slight conjunctivae (score 1, 1, 1), which was still present in 1/3 rabbits at the 24-hour reading time point. The effect had cleared completely within 48 hours. No other eye irritation effects were observed in any rabbit at any time point. The individual mean cornea opacity, iris, and chemosis scores over 24/48/72-hour readings were 0.0 for each rabbit. The individual mean conjunctivae scores over 24/48/72-hour readings were 0.33 in one and 0.0 in two rabbits.Based on the results of this study, the test substance is not considered to be irritating to the eyes.

CAS 72576-80-8

An eye irritation GLP study was performed with Isooctadecyl palmitate (CAS 72576-80-8) according to OECD guideline 405 (supporting study, 1999). 0.1 mL of the unchanged test substance was instilled into one eye of each of 3 male New Zealand White rabbits. The animals were observed for 7 days and scoring according to Draize was performed 1, 24, 48, 72 hours, and 7 days after application. The eyes were not rinsed. At the 1-hour reading time point, 3/3 rabbits had slight-moderate conjunctivae (scores 1, 1, 2) and 2/3 slight chemosis (scores 0, 1, 1). The chemosis had cleared by the 24-hour reading time point, while 3/3 animals still had slight conjunctivae (scores 1, 1, 1). All eye irritation effects were fully reversible within 48 hours. The individual mean cornea opacity, iris, and chemosis scores over 24/48/72-hour readings were 0.0 for each rabbit. The individual mean conjunctivae scores over 24/48/72-hour readings were 0.33 in each of the three rabbits.Based on the results of this study, the test substance is not considered to be irritating to the eyes.

CAS 22766-83-2

2-octyldodecyl myristate (CAS 22766-83-2) was examined for its eye irritation potential in study performed according to a protocol similar to OECD guideline 405 (supporting study, 1982). 0.1 mL of undiluted test liquid test substance was instilled into one eye of each of 6 rabbits. The animals were observed for 7 days and scoring according to Draize was performed 1, 24, 48, and 72 hours as well as 4 and 7 days after application. The individual mean cornea opacity scores over 24/48/72-hour readings were 0.0 for each rabbit. The individual mean iris scores over 24/48/72-hour readings were 0.0 in four rabbits, 0.33 in one and 0.67 in one rabbit. The individual mean conjunctivae scores over 24/48/72-hour readings were 0.0 in five rabbits and 0.33 in one rabbit. The individual mean chemosis scores over 24/48/72-hour readings were 0.0 in two rabbits, 0.33 in three and 0.67 in one rabbit.Based on the results of this study, the test substance is not considered to be irritating to the eyes.

 

Overall conclusion for skin and eye irritation

The available data for the source substances indicate no or only mild skin and eye irritation potential. Thus, no skin or eye irritation potential is expected for the target substance Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5).

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the analogue concept is applied to Fatty acids, C16-18 (even numbered), stearyl esters (CAS 85536-04-5), data will be generated from data for reference source substance(s) to avoid unnecessary animal testing. Additionally, once the analogue read-across concept is applied, substances will be classified and labelled on this basis.

 

The available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008 and are therefore conclusive but not sufficient for classification.